Peptides and therapeutic uses thereof
First Claim
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1. A conformationally constrained compound or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
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Abstract
Conformationally constrained peptides that mimic BH3-only proteins, compositions containing them and their use in the regulation of cell death are disclosed. The conformationally constrained peptides are capable of binding to and neutralising pro-survival Bcl-2 proteins. Processes for preparing the conformationally constrained peptides and their use in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.
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Citations
48 Claims
- 1. A conformationally constrained compound or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
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41. A pharmaceutical composition comprising a conformationally constrained compound, or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
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42. An assay for identifying compounds which bind to a member of the Bcl-2 family of proteins, the assay comprising the steps of:
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(a) providing a candidate compound to be tested;
(b) contacting a Bcl-2 family protein with the candidate compound and a peptide comprising the amino acid sequence;
IAQELRRIGDEFN [SEQ ID NO;
37]under conditions sufficient to allow the candidate compound and the peptide to bind to the Bcl-2 family protein; and
(c) determining whether the candidate compound has bound to the Bcl-2 family protein. - View Dependent Claims (43)
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44. A method of regulating the death of a cell, comprising contacting the cell with an effective amount of a conformationally constrained compound, or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
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45. A method of inducing apoptosis in unwanted or damaged cells comprising contacting said damaged or unwanted cells with an effective amount of a conformationally constrained compound, or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
- 46. A method of treatment and/or prophylaxis of a pro-survival Bcl-2 family member-mediated disease or condition, in a mammal, comprising administering to said mammal an effective amount of a conformationally constrained compound, or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
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48. A method of treatment and/or prophylaxis of a disease or condition characterised by the inappropriate persistence or proliferation of unwanted or damaged cells in a mammal, comprising administering to said mammal an effective amount of a conformationally constrained compound, or a pharmaceutically acceptable salt or prodrug thereof, the compound comprising an amino acid sequence (I):
Specification
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Current AssigneeThe Walter & Eliza Hall Institute Of Medical Research
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Original AssigneeThe Walter & Eliza Hall Institute Of Medical Research
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InventorsBaell, Jonathan
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Application NumberUS10/540,390Publication NumberTime in Patent OfficeDaysField of SearchUS Class Current514/18.900CPC Class CodesA61K 38/00 Medicinal preparations cont...A61P 29/00 Non-central analgesic, anti...A61P 35/00 Antineoplastic agentsA61P 37/00 Drugs for immunological or ...C07K 14/4747 Apoptosis related proteinsC07K 7/02 Linear peptides containing ...
